9.12.3.6 Therapy

•Depending on tumor type:

–When diffuse, infiltrating tumors, prognosis is poor despite therapy

–In focal tumors long-term survival may be 50–90%

•Surgical procedure:

–Tumor resection with low risk of neuroendocrine sequelae

–Morbidity due to is high

–Surgery should be done balancing potential benefits with complications; combined use of irradiation and chemotherapy is commonly used

•Chemotherapy:

–Depends on tumor type

–Palliative therapy (see above)

–Effective drugs and combinations (see above, under “Astrocytic Tumors”)

•Radiotherapy:

–Dose: 40–50 Gy

–Endocrinological observation and substitution therapy as needed

9.12.4Medulloblastoma and PNET

9.12.4.1 Incidence

•Second most frequent brain tumor

•Usually arising from the roof of the fourth ventricle or from the midline structures of the brain

•Dissemination via ventricles and cerebral fluid

•Mean age 4–8 years, range 0–3 and 9–19 years

•Higher frequency in males than females; more common in Caucasians compared to other racial groups

WHO classification (seldomly used)

Medulloblastoma

Desmoplastic/nodular medulloblastoma

Medulloblastoma with extensive nodularity

Anaplastic medulloblastoma

Large cell medulloblastoma

CNS primitive neuroectodermal tumor

CNS neuroblastoma

Medulloepithelioma

CNS ganglioneuroblastoma

Ependymoblastoma

Atypical teratoid rhabdoid tumor (see 9.12.5)

9.12.4.2 Pathology

•Localization: supratentorial 7%, infratentorial 85%, overlapping 3%, not specified 6%

•Highly malignant, small, round blue cell tumor

•Histologically small cells with high rate of mitosis, some in rosette forms; various degree of fibrils

•Degree of differentiation of cells variable and not correlated with prognosis

–Abnormalities of chromosome 17: iso17q in 40%; isolated loss of 17p in 20%; gain in 7 in 40%

–Gene amplification: NMYC at 2q24 amplification in 5–15%

•Histological variants:

–Medulloblastoma with marked stromal components: desmoplastic medulloblastoma in adolescents and adults

–Large cell and/or anaplastic medulloblastoma: about 4% of all medulloblastomas

•High rate of subarachnoid spread: 11–43% initially, in autopsy series, 93% with spread via cerebral fluid

•Extraneural metastatic spread in 4% of patients, especially to bones, lymph nodes, liver, and lung

9.12.4.3 Clinical Manifestation

• Duration of history shorter than in patients with astrocytoma (due to the rapid tumor growth): growth fraction greater than 20%

• High intracranial pressure is an early sign of midline tumors: morning headache, irritability, and lethargy. Infants with unfused fontanels and enlarged head circumference. Fundoscopy: papilledema

9.12.4.4 Radiological Diagnosis

• MRI and CT: midline tumors with marked enhancement. Radiological examination must include spinal canal (dissemination). MRI must be obtained presurgery and 24–48 h postsurgery

9.12.4.5 Therapy

•Surgery:

–Usually preoperative shunt placement for relief of intracranial pressure and reduction of intraand postoperative complications

–Radical resection is often not possible due to the infiltrative nature of the tumor

–Goal of surgery is to remove as much as is safely possible

–Microsurgery improves results

–About 10% of children develop posterior fossa syndromes with transient insomnia and mutism postoperatively

–Analysis of cerebral fluid intraoperatively via lumbar puncture provides important information of tumor dissemination

•Radiotherapy:

–In children less than 3 years of age, irradiation is often delayed and substituted initially with chemotherapy, because of devastating neurocognitive sequelae (see below); this approach has not been shown to compromise outcomes

–Medulloblastoma is radiosensitive